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Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors
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Introduction:

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods:

A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy.

Results:

Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity.

Conclusion:

Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

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Publication Date
Sun Oct 08 2023
Journal Name
European Scholar Journal
THE EFFECT OF AGILE MANUFACTURING STRATEGY ON TOTAL PRODUCTIVE MAINTENANCE
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This research aims to analyze the impact of effective manufacturing strategy on total productive maintenance. Effective manufacturing focuses on improving product quality, increasing productivity, and reducing costs, while total productive maintenance focuses on maintaining machines and equipment in good operational condition and high efficiency. The research seeks to understand how to achieve integration between these two dimensions to achieve excellent performance in manufacturing operations. The study was conducted using the General Company for Battery Manufacturing as a research community, with a sample size of 60 individuals. The research found significant results, including the fact that using an effective manufacturing strategy leads

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Publication Date
Mon Jan 01 2024
Journal Name
Communications In Computer And Information Science
Automatic Identification of Ear Patterns Based on Convolutional Neural Network
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Biometrics represent the most practical method for swiftly and reliably verifying and identifying individuals based on their unique biological traits. This study addresses the increasing demand for dependable biometric identification systems by introducing an efficient approach to automatically recognize ear patterns using Convolutional Neural Networks (CNNs). Despite the widespread adoption of facial recognition technologies, the distinct features and consistency inherent in ear patterns provide a compelling alternative for biometric applications. Employing CNNs in our research automates the identification process, enhancing accuracy and adaptability across various ear shapes and orientations. The ear, being visible and easily captured in

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Publication Date
Thu Sep 30 2021
Journal Name
International Journal Of Research In Social Sciences And Humanities
The Anonymous Identity of Forced Migrants: A Post-Colonial Study
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Colonialism invades the Third World countries, physically and psychologically. This article exposes but sample of the physical and psychological consequences of colonialism. The Beekeeper of Aleppo (2019) by the British novelist, Christy Lefteri is a typical novel to diagnose the harsh circumstances of individuals within and after the disaster. Since it depicts characters from Asian countries, it would be a best representative for all Asian people who suffer colonialism. Migration toward anonymity is the mere option for the colonized people. Aftermath, they experience displacement, trauma, and the loss of identity.

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Publication Date
Mon Mar 08 2021
Journal Name
Baghdad Science Journal
Improving Applied properties of poly unsaturated ester Bozafah monomers Vanalah
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Suggested in this study the introduction of monomers have the ability to interact with polyester Rzn way confused or Alchapak Vodev polycarbonate first Almiaal acrylate ????? grains and offered models for high temperature and for a period of time of 40 days and absorbance and penetration and after color changes resulting from the storage heat higher using shades where models were extractedthermal storage and take measurements and then returned periodically results were consistent with theoretical expectations and mixing

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Publication Date
Sun Jul 01 2018
Journal Name
Journal Of Aerosol Science
On the design of miniature parallel-plate differential mobility classifiers
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Publication Date
Thu Feb 01 2018
Journal Name
Journal Of Computational And Theoretical Nanoscience
Controlling of Robot Hand by Using Microcontroller with Visual Basic
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The robot arm is the most popular robotic form used in industry. Thus, it is crucial to make a system programming which could controlled the movement of each part in the industrial robot to make it works properly. One of the simplest models of the robot arm is EDARM ED-7100 which has a controller to control the movement of the robot arm manually. In this study, the robot controller has been redesigned in order to improve this robot's function. The new controller system used AT89S52 microcontroller which has wire connected to the robot hand. A function has been added with this controller to improve the system of controlling and becomes better than the previous system (only manually). The functions of the new system include three mo

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Publication Date
Sat Jun 30 2012
Journal Name
Al-kindy College Medical Journal
Treatment of Nasopharyngeal Carcinoma by Using Deep X-Ray Therapy
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Background: Nasopharyngeal carcinoma (NPC) is one of the most challenging tumors because of their relative inaccessibility and that their spread can occur without significant symptoms with few signs, but Radiotherapy (RT) has a role in treatment of it.
Objectives: To show that RT is still the modality of choice in the treatment of NPC, to study modes of presentations, commonest histopathological types and their percentages, to show differences in the sensitivities of these types to RT and to find out a 5 year survival rate(5YSR) and its relation with lymph node involvement.
Methods: This is a retrospective study of 44 patients with NPC who were treated with routine RT from 1988-2007 at the institute of radiology and nuclear medicin

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Publication Date
Sat Mar 30 2013
Journal Name
Iraqi Journal Of Chemical And Petroleum Engineering
Studying the Performance of Refrigeration Units Powered by Solar Panel
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An experimental study was conducted to determine the performance of a solar electric refrigeration system. The system contained flat photovoltaic solar panel which absorbs the solar energy and convert it to electrical energy, used to run the refrigeration cycle. Two refrigeration cycles with electrical solar panel were used over a period of 12 months, the first one with classical parts known in refrigeration cycle, while the second one introduced heat exchanger which improves the coefficient of performance by saving the consumed energy. The coefficient of performance of these refrigeration cycles with compressor efficiency 85% are 2.102 and 2.57 respectively. The overall efficiency of the two systems are 18.9% and 23.13%.

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Publication Date
Mon Feb 04 2019
Journal Name
Iraqi Journal Of Physics
Estimation of electron temperature for SiO2 plasma induced by laser
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In this work; Silicon dioxide (SiO2) were fabricated by pulsed
laser ablation (PLA). The electron temperature was calculated by
reading the data of I-V curve of Langmuir probe which was
employed as a diagnostic technique for measuring plasma properties.
Pulsed Nd:YA Glaser was used for measuring the electron
temperature of SiO2 plasma plume under vacuum environment with
varying both pressure and axial distance from the target surface. The
electron temperature has been measured experimentally and the
effects of each of pressure and Langmuir probe distance from the
target were studied. An inverse relationship between electron
temperature and both pressure and axial distance was observed.

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Publication Date
Fri Dec 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
Comparison of some methods for estimating Poisson-Weibull distribution parameters
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In this paper was discussed the process of compounding two distributions using new compounding procedure which is connect a number of life time distributions ( continuous distribution ) where is the number of these distributions represent random variable distributed according to one of the discrete random distributions . Based on this procedure have been compounding zero – truncated poisson distribution with weibell distribution to produce new life time distribution having three parameter , Advantage of that failure rate function having many cases ( increasing , dicreasing , unimodal , bathtube) , and study the resulting distribution properties such as : expectation , variance , comulative function , reliability function and fa

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